In 2007 lung cancer was responsible for 31% of all cancer-related deaths. Advanced stage NSCLC present in 75% of all new lung cancer cases provides a median survival rate of only 9-12 months despite maximal combination chemotherapy. Despite improvements in cancer therapies, the long-term prognosis for patients with metastatic lung cancer remains dismal, and indeed chemotherapy provides only a modest improvement in survival over supportive care alone.
It has been shown that regional and local hyperthermia exhibits synergism with various conventional chemotherapy agents. Hyperthermia selectively kills cancer cells and enhances cytotoxicity of certain chemotherapy drugs, increases tumor blood flow and permeability of tumor blood vessels, and thereby increases drug delivery into a tumor. For example, hyperthermia enhances platinum uptake and inhibits platinum-induce DNA adduct repair, an effect that may be important in reversing cisplatin resistance. Thus, concurrent combined hyperthermia and chemotherapy has great potential in advanced NCSCLC therapy.
Because advanced stage NSCLC patients often have metastasis to remote sites, it is contemplated that systemic hyperthermia would provide advantages over local hyperthermia. Systemic hyperthermia causes marked physiological changes, but damage to normal tissue occurs when temperatures exceed 44 C. Heat has a selective killing effect on malignant phenotypes (lung, colon, and pancreatic cancers, for example) at temperatures between those exhibited during normal fevers and temperatures that induce tissue destruction (41-45 C). This suggests that a hyperthermia therapeutic window may exist for cancer therapy. However, conventional heat delivery such as radiant heat disadvantageously redistributes blood flow away from visceral organs to skin, and peripheral tissue, resulting in heterogenous heat distribution. This leads to insufficient heat delivery to provide a therapeutic benefit, compromising treatment efficiency, and also induces pain and peripheral nerve damage. In turn, conventional veno-venous perfusion-induced hyperthermia systems, because of their relatively long tubing lengths and requiring multiple cannulations (increased circuit lengths), must heat blood to unacceptable temperatures (46 C and above) to provide the desired hyperthermic effect, risking damage to blood cells and pain to the patient.
To solve this and other problems, the present disclosure provides a veno-venous perfusion-induced hyperthermia system (vv-PISH) which delivers more heat to visceral organs for metastatic cancer treatment while eliminating complications and disadvantages of radiant heat. The system includes, a compact heat exchanger including an integral pneumatic pump and blood flow redirector structures. The device of the present disclosure provides an even blood flow pattern, preventing or reducing incidence of thrombosis. In turn, the presently disclosed design simplifies the blood circuit and also provides a pulsatile blood flow pattern, promoting active blood mixing and thereby improving gas exchange within the pump. The present device finds use at least as a supplemental therapy for conventional chemotherapy regimens.